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Epithelial-to-mesenchymal transition (EMT) is thought to play a key role in cancer cell invasion and metastasis. We previously demonstrated that cancer cell migration is inhibited by C-reactive protein (CRP), which is widely used as a biomarker of inflammation, though its functions are not fully understood. In the present study, we evaluated the effect of CRP on cancer cell migration and expression of mesenchymal and epithelial markers of EMT and of related transcription factors. MCA-38 murine colon adenocarcinoma cells were subcutaneously inoculated into the backs of C57BL/6 mice, which also received 1 μg of recombinant mouse CRP or vehicle (phosphate-buffered saline) subcutaneously every 3 days for 4 weeks. Thereafter, the mice were sacrificed for evaluation using quantitative real-time polymerase chain reaction (PCR) and immunohistochemistry. There was no statistical difference in tumor size between the control and CRP groups, but CRP dose-dependently inhibited MCA-38 cell migration. PCR analysis confirmed that CRP suppresses expression of N-cadherin (p < 0.01), a mesenchymal marker of EMT, and ZEB-1, an EMT-related transcription factor (p < 0.01). These findings suggest that CRP inhibits EMT in a MCA-38 tumor-bearing mouse model. CRP may thus be a potentially useful tool for preventing cancer progression through suppression of EMT.

Xanthine dehydrogenase (XDH), also known as xanthine oxidoreductase (XOR), has long been recognized as the key enzyme in the catabolism of purines, oxidizing hypoxanthine into xanthine and then xanthine into uric acid. In addition, levels of XDH expression are reportedly related to the prognosis of patients with malignant tumors, though the relationship between the clinicopathological features of lung cancer and XDH is not fully understood. We therefore used semiquantitative real-time reverse transcription polymerase chain reaction to assess expression of XDH mRNA in tumor samples from 88 patients with adenocarcinoma of the lung. We then correlated XDH mRNA levels with known clinicopathological factors. We found that the 5-year overall survival rate among patients strongly expressing XDH was significantly poorer than among those expressing lower levels of XDH (P < 0.001; log-rank test). Normal lung tissue does not express XDH. Multivariate Cox proportional hazard analyses revealed that being male (hazard ratio, 3.14; 95 % confidence interval (CI), 1.45-7.07; P = 0.004), nodal metastasis positivity (hazard ratio, 5.74; 95 % CI, 1.94-19.3; P = 0.001), and high XDH expression (hazard ratio, 2.33; 95 % CI, 1.11-5.02; P = 0.026) were all independent factors affecting 5-year disease-free survival. In conclusion, high tumoral XDH expression is an independent predictor of a poor prognosis in patients with adenocarcinoma of the lung.

The relation between CCR6 expression and the clinicopathological characteristics of lung cancer and patient prognosis is not well understood and remains controversial. We, therefore, investigated the relationship between CCR6 expression and prognosis in patients with adenocarcinoma of the lung. We used semiquantitative real-time reverse transcription polymerase chain reaction to assess the expression of CCR6 mRNA in tumor samples from 84 patients with adenocarcinoma of the lung. We then correlated the levels of CCR6 mRNA with known clinicopathological features. The 5-year disease-free survival rate among patients expressing higher levels of CCR6 mRNA was significantly better than among those expressing lower levels (P = 0.009 by log-rank test). Multivariate Cox proportional hazard analyses revealed, being male [hazard ratio, 3.94; 95% confidence interval (CI), 1.58 to 10.36; P = 0.003], tumor size >30 mm (hazard ratio, 2.46; 95% CI, 1.08 to 5.73; P = 0.030), nodal metastasis (hazard ratio, 7.66; 95% CI, 2.62 to 23.3; P = 0.0002), and CCR6 (hazard ratio, 0.34; 95% CI, 0.11 to 0.93; P = 0.034) to be independent factors affecting the 5-year disease-free survival rate. Greater expression of CCR6 by tumor cells is an independent predictor of a better prognosis in patients with adenocarcinoma of the lung.